Lower alkyl 3-hydroxy and 3-mercaptopyrazinoates

ABSTRACT

LOWER ALKYL 3-HYDROXY- AND 3-MERCAPTO-PYAZINOATES AND CORRESPONDING ETHERS AND THIOETHERS ARTE PREPARED BY DIAZOTIZATION OF LOWER ALKYL 3-AMINOPYRAZINOATES FOLLOWED BY TREATMENT WITH WATER TO GIVE THE 3-HYDROXY COMPOUNDS, OR AN ALCOHOL TO GIVE THE 3-ETHER COMPOUNDS AND WITH BROMINE AND HYDROGEN BROMIDE TO GIVE THE 3-BROMO COMPOUNDS. THE LATTER COMPOUNDS ARE THEN CONVERTED INTO THE 3/MERCAPTO COMPOUNDS BY TREATMENT WITH SODIUM SULFIDE AND SULFUR OR INTO THE 3-THIO-ETHERS BY TREATMENT WITH AN ALKALI METAL MERCAPTIDE, THE COMPOUND ARE USEFUL AS INTERMEDIATES FOR THE PREPARATION OF THE CORRESPONDING PYRAZINOYLGUANIDINES WHICH HAVE UTILITY AS DIURETIC AND SALURETIC COMPOUNDS.

United States Patent US. Cl. 260-250 R Claims ABSTRACT OF THE DISCLOSUREThis application is a division of our copending application S.N.594,996, filed Nov. 17, 1966'now US. Patent 3,472,848, issued Oct. 14,1909, the entire disclosure of which is incorporated herein byreference.

SUMMARY OF THE INVENTION This invention relates to lower alkylpyrazinoates of the following structural formula:

N YT IZ X C OO-lower alkyl wherein Z represents (a) OR wherein Rrepresents (1) hydrogen, (2) loweralkyl of from 1 to 5 carbon atoms, (3)phenyl-lower alkyl, and

(b) SR wherein R represents (1) hydrogen, (2) loweralkyl of from 1 to 5carbon atoms, (3) aralkyl, such as benzyl and phenethyl, and (4) aryl,preferably phenyl;

X represents (a) hydrogen,

(b) halo such as chloro, bromo and iodo,

(c) loweralkyl of from 1 to 5 carbon atoms, (d) lower cycloalkyl of from3 to 6 carbon atoms, and

(e) mononuclear aryl, especially phenyl either unsub- 50 stituted orsubstituted preferably with halogen such as chloro or bromo;

Y represents (a) hydrogen, (b) hydroxy, (c) lower-alkoxy of from 1 toabout 5 carbon atoms,

3,660,400 Patented May 2, 1972 Fee (d) lower-alkylthio of from 1 toabout 3 carbon atoms,

(e) loweralkyl of from 1 to about 5 carbon aatoms,

(f) w,w,w-trifluorolower-alkyl such as trifluoromethyl, trifluoroethyland the like,

(g) lower-cycloalkyl having 3 to 6 carbons, and

(h) mononuclear-aryl, preferably phenyl;

X and Y can be linked together to form a 4-membered carbon chain eitherunsaturated or saturated, either unsubstituted or substituted with, forexample, a halogen to form compounds such as tetrahydroquinoxaline orquinoxaline derivatives.

The novel compounds of this invention wherein Z represents OR" areprepared by diazotization of the correspondi'ng loyer alkylB-aminopyrazinoates, followed by treatment of the diazotization mixturewith water (R' =H) or an alcohol of formula R"OH.

Where Z represents SR in the novel compounds they I are prepared bydiazotization of the corresponding lower alkyl 3-aminopyrazinoates in amixture of bromine, hydrobromic acid and acetic acid to provide thelower alkyl 3-bromopy-razinoates which are then converted to thecorresponding 3-mercapto compounds (R =H) by treatment with a mixture ofsodium sulfide and sulfur, and the 3-substituted thio compounds bytreatment with an alkali metal mercaptan (e.g., NaSR).

The novel compounds of this invention are useful intermediates in thepreparation of 3-Z-pyrazinoylguanidines which have utility as diureticand saluretic agents in the treatment of edema, hypertension and otherdiseases known to be responsive to diuretic therapy.

What is claimed is:

1. A compound of structural formula N Y- Z X N -C OO-lower alkyl wherginZ is a member selected from the group consistmg 0 (a) 0R", wherein R isa member selected from the group consisting of (1) hydrogen, (2)lower-alkyl, (3) phenyl lower-alkyl, and

(b) SR wherein R is a member selected from the,

3 4 X and Y can be linked together to form with the pyra- ReferencesCited zgirelpglllcrlligty a quinoxaline or tetrahydroquinoxaline UNITEDSTATES PATENTS 2. A compound as claimed in claim 1, wherein Z is3,472,348 10/1969 Cfagoe et 260-250 0 'z 5 3,527,759 9/1970 Shepard260250 3. A compound as claimed in claim 2, wherein X is NICHOLAS RIZZO,Primary Examiner halogen.

4. A compound as claimed in claim 1, wherein Z is U.S. Cl. X.R. 42 2s0 15. A compound as claimed in claim 4, wherein X is 10 halogen.

